The goals of this project are to detect and accurately describe peri-menopausal mood disorders, explore their pathophysiology and response to pharmacological and environmental manipulation, and to document the relationship between reproductive endocrine change and disorders of mood as a way of further investigating the neurobiology of psychiatric illness. Findings to date include: 1) preliminary evidence of the therapeutic efficacy of estrogen in ten peri-menopausal women with non-hot flush-related depressions; 2) absence of evidence of abnormal response to TRH stimulation in peri-menopausal depressed women compared with controls; 3) preliminary evidence of the spontaneous reversal of ovarian insensitivity-related depression and hot flushes in peri-menopausal women; 4) significant clomiphene citrate-induced elevations of FSH and decreases of estradiol in women with irregular menstrual cycles compared with age-matched, regularly cycling controls.